Interstitial fibrotic lung disease is commonly found in humans exposed occupationally and environmentally to certain inorganic particles. We have established animal models to elucidate the initial cellular events associated with inhalation of the toxic dusts, asbestos and silica, and we have determined that a variety of inorganic particles, regardless of shape or concentration, deposits initially at bifurcations of alveolar ducts. It is at these sites of particle deposition that we have documented the earliest anatomic alterations induced by inhalation of asbestos fibers. These alterations at duct bifurcations include (1) phagocytosis of asbestos fibers by the alveolar epithelium, (2) translocation of fibers through the epithelium to capillary spaces and interstitial connective tissue, (3) phagocytosis of fibers by interstitial fibroblasts, (4) formation of interstitial intracellular microcalcifications, and (5) accumulation of alveolar and interstitial macrophages. Now, we report the following: (1) One month after a 1-hr exposure to chrysotile asbestos, the alveolar duct bifurcations exhibited normal epithelial cells, but there were significant increases in the numbers of interstitial fibroblasts and macrophages and in the amount of interstitial extracellular matrix, some of which was collagen. (2) Autoradiographic studies demonstrated that increased numbers of epithelial cells lining terminal bronchioles as well as epithelial and interstitial cells of alveolar duct bifurcations incorporated tritiated thymidine into DNA. (3) One month after the 1-hr exposure to asbestos, 19% of the fibers which had originally been deposited after inhalation was still present in the interstitium of the rats' lungs. Further studies are ongoing to establish the role of interstitial fibers and the mechanisms through which the fibers induce fibroblast proliferation and collagen production.